Abstract
NLRP6 inflammasome, one of the important intracellular innate immune sensors, has been shown to regulate immune responses. However, its roles in the intracerebral hemorrhage (ICH) are completely not clear. In the present study, we investigated the expression profile and biological roles of NLRP6 inflammasome in perihematomal brain tissues of mice subjected to ICH. In this study, we investigated the expression profile of NLRP6 inflammasome in the perihematomal brain tissues and explored the biological role of NLRP6 inflammasome upon acute brain injury in mice subjected to ICH. Increased expression of NLRP6 inflammasome was found in perihematomal brain tissues ranging from 6 h to 3 days, with a peak level at 1 day after ICH. Immunohistochemistry staining also showed that NLRP6 inflammasome was significantly increased in the perihematomal brain tissues at 1 day after ICH. Moreover, immunofluorescence staining showed that NLRP6 inflammasome was mainly colocalized in glial fibrillary acidic protein (GFAP)-positive astrocytes, while with little colocalized expression in NeuN-positive neurons and without expression in CD11b-positive microglia and CD31-positive endothelial cell in the perihematomal brain tissue of mice after ICH. Furthermore, NLRP6−/− ICH mice exhibited significantly higher brain water contents (BMCs), proinflammatory cytokines, NF-κB activity and neurological deficit scores when compared with the wild type (WT) ICH mice. In addition, we found that Toll-like receptor 4 (TLR4)−/− mice, as well as the TAK242 treated mice, had markedly lower expression of NLRP6 inflammasome expression in the perihematomal brain tissue at 1 day after ICH. Our data suggest that the upregulated NLRP6 inflammasome in perihematomal brain tissues attenuates ICH-induced brain injury.
Highlights
Intracerebral hemorrhage (ICH) is characterized by high mortality and morbidity and accounts for 23.8% of all strokes in China (Zhou et al, 2014; Wang et al, 2017)
We found that NLRP6 inflammasome expression was markedly increased at 1 day after intracerebral hemorrhage (ICH) compared with the normal brain (NS) and sham groups, while the upregulation of NLRP6 inflammasome was gradually decreased from 3 days after ICH (Figure 1A)
glial fibrillary acidic protein (GFAP)-positive astrocytes appeared to be the major source of NLRP6 inflammasome expression after ICH, in contrast, little NLRP6 inflammasome expression was detected in NeuN-positive neurons or without expression in CD11bpositive microglia and CD31-positive endothelial cell (Figure 3)
Summary
Intracerebral hemorrhage (ICH) is characterized by high mortality and morbidity and accounts for 23.8% of all strokes in China (Zhou et al, 2014; Wang et al, 2017). The enhanced production of proinflammatory cytokines released by activated glial cells and infiltrated leukocytes after ICH was the major reasons for inflammatory injury (Mracsko and Veltkamp, 2014; Wei et al, 2014; Zhong et al, 2016). Among these proinflammatory cytokines, interleukin (IL)-1β is considered as a pivotal therapeutic target in NLRP6 Ameliorates Brain Injury after ICH. Inflammasome, as one of the intracellular innate immune sensors, has been shown involved in the pathogenesis of sterile inflammatory response following central nervous system (CNS) disorders, such as traumatic brain injury (Tomura et al, 2012), ischemic stroke (Abulafia et al, 2009) and ICH (Ma et al, 2014)
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